IgM serum antibodies to phenolic glycolipid-I and clinical leprosy: two years' observation in a community with hyperendemic leprosy

A village population with hyperendemic leprosy in Papua New Guinea was repeatedly examined for clinical leprosy and for serum IgM antibodies to phenolic glycolipid-I (APGL-I) over 2 years between 1984 and 1986. In 1984, serum APGL-I was elevated in 15% of the subjects without clinical leprosy, and the prevalence of seropositivity was not significantly different in subjects from households with or without leprosy. In 1986, the prevalence of elevated serum APGL-I in leprosy-free subjects had risen to 23%. The incidence of seroconversion from APGL-I negative to APGL-I positive was 9.5% per year (95/1000 person years) in 253 subjects tested in 1984 and 1986. During the same period, 27 of 40 (67%) leprosy-free subjects reverted from positive to negative. The positive seroconversion rate in the community was higher than the incidence of clinical leprosy (11.2/1000 person years) over the same period. However, elevated serum APGL-I was not associated with clinical disease and failed to predict the development of disease over 2 years. The significance of persistent seropositivity found in 14 (5%) leprosy-free subjects is uncertain.     

Inhibition of phenolic glycolipid-I synthesis in extracellular Mycobacterium leprae as an indicator of antimicrobial activity

The effects of 22 antimicrobial agents on the incorporation of [U14C] palmitic acid ([U14C] PA) into the unique phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were studied. Nude-mouse-propagated M. leprae were incubated in a modified Dubos medium in the presence of antimicrobial agents for 4 days. [U14C] PA was then added and incubation was continued for 8 days. The antileprosy agents dapsone, rifampin, and clofazimine (2 micrograms/ml each) caused a significant reduction in [U14C] PA incorporation into PGL-I. Among other agents, the most active were erythromycin, chloramphenicol, and cerulenin. Low concentrations of ethionamide, tetracycline, and minocycline stimulated label incorporation. This system may prove useful in the evaluation of antileprosy agents.     

Sequential monitoring of leprosy patients with serum antibody levels to phenolic glycolipid-I, a synthetic analog of phenolic glycolipid-I, and mycobacterial lipoarabinomannan

Sequential serum samples from leprosy patients at various stages of antibacterial treatment were tested by an ELISA for antibodies to phenolic glycolipid I (PGL-I), a synthetic PGL-I analog (ND-BSA), and lipoarabinomannan (LAM) from Mycobacterium tuberculosis to determine if these antibodies could be useful in monitoring response to therapy. Among patients with positive initial anti-PGL-I IgM, a significant decrease in this antibody was seen over time (p less than 0.01), whether assayed by PGL-I or ND-BSA. The two antigens showed good agreement in the detection of decrease in anti-PGL-I IgM. The greatest decrease was seen in patients with a high initial anti-PGL-I IgM and a high bacterial index (BI). Patients with a declining BI were seen to have generally declining antibody levels to PGL-I and to LAM; in those patients with a fluctuating BI, antibody levels were less predictable. We conclude that antibodies to PGL-I and LAM can be useful in following response to therapy in leprosy patients and that either the native PGL-I or ND-BSA can serve as antigen for the ELISA.     

IgM antibodies to native phenolic glycolipid-I in contacts of leprosy patients in Venezuela: epidemiological observations and a prospective study of the risk of leprosy

In a randomized, double-blind vaccine trial in Venezuela, about 29,000 contacts of leprosy patients have been vaccinated with either a mixture of heat-killed Mycobacterium leprae and BCG or BCG alone, and are being re-surveyed annually to detect new cases of leprosy. All contacts had a serum sample collected at the time of entry into the trial, and 13,020 of these sera have been analyzed for antibodies to phenolic glycolipid-I (PGL-I). Antibody levels have been related to various characteristics of the contacts and to their risk of developing leprosy in the following 4 years. A strong association was found between PGL-I antibody level and the risk of developing leprosy, in spite of possible modification of the incidence rate induced by vaccination. Antibody levels were higher in females than in males, and declined progressively with age. Household contacts had higher levels than did non-household contacts, and levels were higher in individuals from the state in Venezuela which has the highest incidence of the disease. No substantial differences were found in antibody levels between contacts of multibacillary and paucibacillary patients, which may in part reflect the influence of treatment, and there was no clear association with the presence of BCG or lepromin scars or with skin-test responses to PPD and leprosy soluble antigen. The assay of antibodies to PGL-I seems unlikely to provide a sensitive or specific test for infection with M. leprae, and measuring PGL-I antibody levels as a screening procedure to identify those at high risk of developing leprosy is unlikely to be particularly useful in most leprosy control programs. Such assays may be useful for the epidemiological monitoring of changes in the intensity of infection with M. leprae in a community and for the study of carefully defined groups of contacts during some phases of control programs.     

ELISA detection of IgM antibodies against phenolic glycolipid-I in the management of leprosy: a comparison between laboratories

IgM antibodies to the phenolic glycolipid-I (PGL-I) antigen of Mycobacterium leprae were detected by different ELISA techniques in three laboratories (in New York, Colorado, Seattle, U.S.A.). The agreement on seropositivity and overall correlation between techniques was excellent. A positive linear correlation between the bacterial index (BI) and anti-PGL-I IgM, previously reported by the New York laboratory, was detected by all techniques. The role of erythema nodosum leprosum in decreasing the relationship of BI versus anti-PGL-I IgM was seen by the New York laboratory with sera diluted 1:20 and ABTS substrate solution and by the Colorado laboratory but not by New York with sera at 1:300 and OPD substrate or by the Seattle laboratory.     

Serologic responses to Mycobacterium leprae-specific phenolic glycolipid-I antigen in sooty mangabey monkeys with experimental leprosy

Four pairs of sooty mangabey monkeys (Cercocebus atys) were inoculated with serial, 10-fold dilutions of Mycobacterium leprae. The highest-dose pair received 4.8 X 10(10) M. leprae. Serum samples were obtained and clinical signs of leprosy were recorded at intervals of 35 months. Longitudinal serum samples were assayed by an ELISA method for the presence of IgG and IgM antibodies to the M. Leprae-specific phenolic glycolipid-I (PGL-I) antigen. In general, the onset of disease symptoms paralleled the number of M. leprae inoculated, but the ultimate course of disease depended upon individual animal susceptibility. Both IgG and IgM anti-PGL-I isotypes were observed in variable levels and patterns, related to the disease stage, among the eight mangabeys. The data suggest that high IgG and low IgM anti-PGL-I levels correlated with less severe disease; whereas initial high IgM titers and/or rising or sustained high IgM titers, especially together with low IgG anti-PGL-I titers, preceded or corresponded to periods of progressive leprosy. The results show that IgG and IgM anti-PGL-I antibodies can be present in significant titers among mangabeys early after infection with M. leprae. It appears likely that the relative levels of these anti-PGL-I isotypes may be correlated with the susceptibility of individual animals to the development of lepromatous leprosy.     

Serum IgA1 and IgM antibodies against Mycobacterium leprae-derived phenolic glycolipid-I: a comparative study in leprosy patients and their contacts

In order to evaluate the potentials of IgA1 versus IgM as well as of native phenolic glycolipid-I (PGL-I) versus PGL-I-disaccharide coupled to bovine serum albumin (D-BSA) as antigens in the serodiagnosis of leprosy, anti-D-BSA IgA1 and anti-PGL-I IgM were investigated and compared to anti-PGL-I IgA1 in sera from patients and contacts. Anti-D-BSA and anti-PGL-I IgA1 significantly correlate in patients and contacts. The higher IgA1 positivity rates obtained with D-BSA as compared to PGL-I may suggest D-BSA as the favorable antigenic material. In patients but not in contacts anti-PGL-I IgM and IgA1 correlate, IgM predominating over IgA1. In all three antibody systems, the mean values as well as the positivity rates increased from the tuberculoid toward the lepromatous disease pole. Also, the levels of all three antibodies significantly increased with the bacterial index (BI). However, anti-D-BSA (PGL-I) IgA1 appears to be preferable to IgM with respect to sensitivity, i.e., detection of disease activity, in paucibacillary or BI-negative patients. A number of contacts were detected as seropositive with anti-D-BSA and/or anti-PGL-I IgA1 but not with anti-PGL-I IgM. This suggests that IgA1 is a better tool than IgM for the detection of leprosy in its subclinical stage.     

Seroprevalence of antibodies to parvovirus B19 among children in Papua New Guinea

Parvovirus B19 (B19) is a common childhood infection that has recently been found to be associated with severe anemia in Papua New Guinean children. Population surveys were performed in 15 villages in Maprik district, East Sepik Province, Papua New Guinea in 2005. Plasma samples collected from children less than 10 years of age were tested for IgM and IgG antibodies to B19 by enzyme immunoassay. The prevalence of IgG antibody to B19 was 53.8% and ranged from 20% in those less than one year of age to 85.5% in those nine years of age. Considerable variation in IgG prevalence was observed between study areas, indicating complex patterns of transmission. Prevalence of IgM antibody to B19 was 1.5%. This study confirms that B19 infection is common among children in this tropical area. With 19.5% of children one year of age showing evidence of previous infection, any preventive measures should be targeted at the very young.     

Use of anti-M. leprae phenolic glycolipid-I antibody detection for early diagnosis and prognosis of leprosy

Untreated patients suffering from tuberculoid, lepromatous and indeterminate leprosy, their domiciliary contacts, and healthy controls, all living in Guadeloupe, West Indies, were tested by an ELISA for detecting IgM antibodies to the terminal disaccharide of the phenolic glycolipid-I antigen of Mycobacterium leprae. On most subjects, a Mitsuda test was also performed. A large majority of the tuberculoid patients and healthy subjects were Mitsuda positive. The seropositivity rate reached 44% among tuberculoid patients, and 6% among healthy subjects, with low antibody levels. Lepromatous patients were all Mitsuda negative and seropositive, with antibody production varying from low levels, as seen in tuberculoid patients, to much higher levels. Indeterminate leprosy patients included 62% Mitsuda-positive subjects and 54% seropositive subjects with a large dispersion of antibody levels. Comparing the results of the Mitsuda test to those of the ELISA by factorial analysis allowed us to define several subgroups among this population: some (25%) showed a "lepromatous-like" immune status (Mitsuda negative, seropositive); others (54%) exhibited "tuberculoid-like" profiles (Mitsuda positive without antibodies or with low antibody levels). "Lepromatous-like" cases were significantly older than "tuberculoid-like" patients. A group of subjects (17%) was Mitsuda negative and seronegative, thus displaying a true "indeterminate" immune profile, which had not been seen in other forms of the disease and had been observed in only 2 out of 51 healthy controls. A large majority of contacts was Mitsuda positive, with 33% of them being seropositive, indicating that the prevalence of M. leprae infection greatly exceeds that of overt leprosy in this population.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibodies to a synthetic analog of phenolic glycolipid-I of Mycobacterium leprae in healthy household contacts of patients with leprosy

Fifty-four household contacts of lepromatous patients, 39 household contacts of tuberculoid patients, and 99 control persons were examined with an enzyme-linked immunosorbent assay for their antibody responses to phenolic glycolipid-I (PGL-I) of Mycobacterium leprae using a synthetic analog (PGL-ISA) with the same terminal sugar epitope, namely, O-(3, 6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(alpha-L-rhamnopyranosyl )-(1----9)-oxynonanoyl-BSA. This study was conducted in the Gurage area of Ethiopia in 15 households with a leprosy patient and 15 matched control households. Household contacts with more than 1 year of exposure to a lepromatous patient had antibodies to PGL-ISA significantly more often (19 of 34 persons) than did household contacts with less than 1 year of exposure to a lepromatous patient (4 of 20 persons), household contacts of tuberculoid patients (8 of 39 persons), and persons without exposure to leprosy in the household (33 of 99 persons). No significant association was found between the prevalence of antibodies to PGL-ISA in the household contacts and disease activity in the lepromatous index patients at the time of examination; nor was there a significant association between antibody responses and age or sex of the contacts. The increased prevalence of antibodies to M. leprae antigen in healthy persons with more than 1 year of contact with a lepromatous patient provides further evidence that subclinical infection in leprosy is common, and is related to the type of leprosy in the index patient. The fact that antibodies to PGL-ISA were detected in one third of the persons without household exposure to leprosy emphasizes the necessity to always include comparable controls from the same endemic area in studies of leprosy contacts.     

Evaluation of an improved approach using residences of schistosomiasis-positive school children to identify carriers in an area of low endemicity

School children were used as indicators for the identification of schistosomiasis-positive family members in a area of low endemicity. This study was designed to improve current schistosomiasis control programs by applying this strategy to identify schistosomiasis-positive individuals in a more efficient way. The initial prevalence among school children was 8.6%. However, the prevalence among the family members of these school children increased to 15.5%. In contrast to these findings the prevalence in family members of schistosomiasis-negative school children was 3.8%. Although the applied methodology showed a relatively low sensitivity (50.0%), the high negative predictive value (87.7%) indicates that a few positive family members of school children with a negative stool result will be missed. This shows that this method of evaluation could be a strategy for a more efficient and cheaper identification of schistosomiasis-positive individuals in areas of low endemicity.     

Seroprevalence of varicella antibodies among new house officers

STUDY OBJECTIVE: Varicella, an illness common to children, can occur in nonimmune adults, often causing serious morbidity and mortality. House officers without protective titers to varicella are at risk of contracting the disease and may spread it to the patients they serve. They are also subject to significant losses in work time and wages. Accordingly, in August 1996, the Centers for Disease Control and Prevention recommended vaccinating nonimmune health care providers with the varicella vaccine. We also sought to document the seroprevalence of varicella antibodies among new house officers and to determine the association of self-reported history of infection with varicella antibody levels. METHODS: This study was conducted at a university-affiliated teaching hospital. Serology testing was performed on house officers beginning their residencies in July 1997. Subjects provided information regarding demographics, medical history, previous varicella exposure, and previous administration of varicella vaccine. Serum was tested using the FIAX test kit, (Biowhitaker, Walkersville, MD). RESULTS: One hundred fifty-four house officers participated. The mean age was 30 (range, 24 to 50+/-SD 5.5 years). History of varicella infection was given by 119 (77%) of the 154 subjects, whereas 15 (10%) reported no history of infection, and 20 (13%) were uncertain. Ten (7%) of the participants had received varicella vaccine previously. Overall, 6 (4%) had nonprotective titers to varicella. Of the 119 house officers who reported a history of varicella, only 2 (1.7%) had nonprotective titers, and 4 (27%) who reported no history of varicella infection had nonprotective titers. Of the 10 house officers who had previously received varicella vaccine, 1 (10%) had nonprotective titers. CONCLUSION: Although most house officers had protective titers, a reported history of varicella or the administration of varicella vaccine did not assure the presence of protective titers. House officers should be tested for varicella immunity regardless of a history of previous infection or the administration of varicella vaccine.     

Seroprevalence of dengue antibodies, annual incidence and risk factors among children in southern Vietnam

Dengue is highly endemic in southern Vietnam and all four serotypes of dengue virus have already been identified. To determine the age-specific prevalence of dengue and associated risk factors, we conducted a serological study at two primary schools and assessed risk factors by analysing children's questionnaires and household surveys. Sera were collected from 961 primary schoolchildren in Binh Thuan Province and tested for the presence of dengue virus serum antibodies using an indirect immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA). The antibody prevalence of the total population was 65.7% (n=631) which increased from 53.0 to 88.2% with age. The annual incidence of a first dengue infection, estimated by binary regression of the seroprevalence by age, was 11.7%. Interestingly, the prevalence of dengue IgG antibodies was significantly higher in children who confirmed using a pit latrine (RR 1.467, 95% CI: 1.245-1.730) and whose domestic environment contained discarded cans (RR 1.238, 95% CI: 1.042-1.470) and pigs (RR 1.228, 95% CI: 1.002-1.504). The epidemiology of dengue in southern Vietnam is stable with a constantly high annual incidence of first infections. Transmission occurs mainly peri-domestically, which has important public health implications.     

Seroprevalence of anti-cysticercus antibodies among the children living in the urban environs of Maputo,Mozambique

Blood and faecal samples were collected from 269 children (aged 0-15 years) who lived in the urban environs of Maputo, the capital city of Mozambique. Antibodies against Cysticercus cellulosae were detected, at a titre of at least 1:100, in 56 (20.8%) of the blood samples. When the stool samples were checked for Taenia solium and other helminths, both as direct smears and after formalin-ether concentration, 180 (67.0%) were found to contain at least one helminth species. The parasites most commonly detected in the faecal samples were Trichurus trichiura (36.0%) and Ascaris lumbricoides (35.7%). Only in one sample (0.4%) were gravid proglottids of Ta. solium detected, but Hymenolepis nana (1.1%) and H. diminuta (0.4%) were also found. A positive correlation between seropositivity for anti-cysticercus antibodies and subject age, and positive associations between such seropositivity and infection with A. lumbricoides and infection with Tr. trichiura were observed. None of the other demographic and environmental factors investigated--the child's sex, religion and access to toilets and/or piped water, the type of house in which he or she lived, the number of individuals in the household to which he or she belonged, and whether that household had pets or raised livestock--showed any apparent association with either the seroprevalence of anti-cysticercus antibodies or infection with any intestinal helminth. The use of water from the common sewage-drainage system for agricultural irrigation in the study area probably causes most of the contamination with intestinal parasites.     

Seroprevalence of rubella antibodies among pregnant females in Sri Lanka

The purpose of this study was to determine the seroprevalence of rubella antibodies among pregnant females in the Kalutara District of Sri Lanka, and to identify factors associated with susceptibility to rubella infection among pregnant females. A cross-sectional clinic-based study was conducted among 620 pregnant women attending antenatal clinics and residing in the district for more than one month. Data on the pregnant females and the socio-economic characteristics of the families were obtained using an interviewer-administered structured questionnaire. Three milliliters of blood was obtained to measure rubella-specific IgG antibody levels by ELISA (enzyme linked immunosorbent assay) tests. Overall, 76% of pregnant females were seropositive for rubella antibodies. Seropositivity in pregnant females increased with age. Susceptibility to rubella was significantly associated with rubella immunization status. Given the high susceptibility rate to rubella infection among pregnant females, it is imperative that any vaccination strategy in the short-term should focus on reducing the number of susceptible women of child-bearing age.